Equilibrium Structure Research Articles

In search of suitable protein targets for anti-malarial and anti-dengue drug discovery

Selecting suitable targets is the critical first step in drug discovery. However, for malaria and dengue this is quite a challenging step due to a large number of available structures for every disease targets, about 139 crystal structures for dengue and 367 structures for malaria. This study employed a combination of druggability filtering and computational analysis through molecular docking and molecular dynamics (MD) simulations in oder to select suitable drug targets for dengue and malaria. Initially, diverse target structures for dengue and malaria in Protein Data Bank were assessed for their druggability and as the result, druggable targets were chosen. There were three potential druggable targets NS5, NS3 and NS2B-NS3 protease for dengue, and several targets involved in the food vacuole, apicoplast, mitochondria, cytosol, phosphatidylcholine synthesis pathways for malaria. Molecular docking of co-crystallised ligands with these targets was carried out and the complexes of targets satisfied with high binding affinies and RMSD values were selected. Subsequently, MD simulations of these complexes were run for 100 ns and different conformational structures of target proteins during the period of time were extracted for ensemble docking for each target. Re-docking results showed a significant difference in using equilibrium structures and initial structures from PDB. Finally, the suitable target structures were selected, including NS5 MTase for dengue and plasmepsin for malaria which can be used for further drug design studies.

Relaxation of multi-ion plasmas in an internal conductor

The possibility of the formation and characteristics of the relaxed structures in the multi-ion magnetized plasmas consisting of heavy ions, light ions, and inertia-less electrons have been explored. Using the vortex dynamic equations with the current density, the system is relaxed to triple Beltrami states. Solutions of the relaxed states are determined in two different cases: (i) simple slab geometry and (ii) slab geometry with an internal conductor. The impact of Beltrami parameters and density ratios of the plasma components on the formation of equilibrium structures in both geometries has been studied. Moreover, we also highlight the equivalences of both geometries (simple slab geometry and a slab geometry with an internal conductor). This investigation will be useful for studying and understanding the relaxed structures in different astrophysical objects such as solar wind, Earth’s ionosphere, near-Earth plasmasheet, upper ionosphere, and Saturn and in the laboratory plasmas having two positively charged ions of different masses. Moreover, this work will be helpful in describing the underlying physics of the relaxed structures. These structures are developed in different astrophysical bodies that revolve around the planet such as Jupiter magnetosphere.

Current structure predictors are not learning the physics of protein folding.

Summary Motivation. Predicting the native state of a protein has long been considered a gateway problem for understanding protein folding. Recent advances in structural modeling driven by deep learning have achieved unprecedented success at predicting a protein’s crystal structure, but it is not clear if these models are learning the physics of how proteins dynamically fold into their equilibrium structure or are just accurate knowledge-based predictors of the final state. Results. In this work, we compare the pathways generated by state-of-the-art protein structure prediction methods to experimental data about protein folding pathways. The methods considered were AlphaFold 2, RoseTTAFold, trRosetta, RaptorX, DMPfold, EVfold, SAINT2 and Rosetta. We find evidence that their simulated dynamics capture some information about the folding pathway, but their predictive ability is worse than a trivial classifier using sequence-agnostic features like chain length. The folding trajectories produced are also uncorrelated with experimental observables such as intermediate structures and the folding rate constant. These results suggest that recent advances in structure prediction do not yet provide an enhanced understanding of protein folding. Availability. The data underlying this article are available in GitHub at https://github.com/oxpig/structure-vs-folding/Supplementary information Supplementary data are available at Bioinformatics online.

Structural Basis of the Selective Sugar Transport in Sodium-Glucose Cotransporters

Sodium-glucose cotransporters (SGLTs) are responsible for sugar absorption in small intestine and renal tubule epithelial cells. These proteins have attracted clinical attention as a cause of malabsorption and as a target for diabetes drugs. Each SGLT isoform has strict selectivity for its monosaccharide substrate. Few studies have attempted to elucidate the structural basis of sugar selectivity by allowing generating SGLT mutants that bind substrates not normally transported or by reproducing the substrate specificity of other isoforms. In this study, we built a structural homology model for the substrate binding states of human SGLT1 (hSGLT1), which primarily transports glucose and galactose. We also performed electrophysiological analysis of hSGLT1 using various natural sugars and mutants. By mutating the K321 residue, which forms hydrophilic interactions in the sugar binding pocket, we induced mannose and allose transport. We also changed the glucose/galactose transport ratio, which reproduces the substrate specificity of the prokaryotic galactose transporter. By adding mutations one-by-one to the residues in the binding pocket, we were able to reproduce the substrate specificity of SGLT4, which transports fructose. This suggests that fructose, which exhibits various structures in equilibrium, binds to SGLT in a pyranose conformation. These results reveal one state of the structural basis that determines selective transport by SGLT. These findings will be useful for predicting the substrates of other glucose transporters and to design effective inhibitors.

Inward‐looking policies, finite change, and employment: The capital reallocation effect

AbstractIt is well recognized that there emerged a trend of inward‐looking trade policies even before the COVID pandemic crippled the world. These were reflected in both BREXIT and US‐China trade conflicts. As countries become inward‐oriented, usually local prices start rising. With this backdrop, this paper explores how rising local prices are likely to affect employment in the short and long runs when we accommodate for the finite change in a general equilibrium structure whereby sectors not only contract but might also close down altogether due to the capital reallocation effect following a price incentive.

First-principles calculations to investigate stability, electronic properties and anisotropy of half-metallic full Heusler alloy Co2NbGa

The phase structures, magnetic properties, electronic structures, and anisotropy of the full Heusler alloy Co2NbGa were studied using the first-principles method, and the results were compared with experiments. The L21-type cubic structure was the most stable, which was in good agreement with the experimental measurement. The Curie temperature obtained by the mean field theory was also very close to the experimental value. The electronic structures and magnetic properties showed that the Co2NbGa alloy was a half-metallic ferromagnet with 100% spin polarization at equilibrium, and the robustness of the half-metallic feature was preserved in lattice ranges of 5.79 to 6.42 Å. The Co2NbGa alloy was an anisotropic material with stable mechanical properties at L21-type cubic and XA-type tetragonal structures, and the influence of Hubbard U and vacancy defects on the physical nature was also studied and discussed. The 100% spin polarization, high Curie temperature, and stable equilibrium structure make Co2NbGa alloy a promising candidate in spintronics and magnetoelectronic.

An exotic microstructured globular state formed by a single multiblock copolymer chain.

In this work, we studied the equilibrium structures formed by a single (AB)k multiblock copolymer chain. Within our model, the interactions between the A-type beads were repulsive and the B-type beads could form pairwise reversible bonds with each other (BB-bonds). Our goal was to investigate how the formation of pairwise reversible bonds between the A-type beads and the B-type beads (AB-bonds) affected the structure of the chain. We observed the formation of well-studied intramolecular micelles when the AB-bonds were absent; however, the chain folding changed dramatically when the formation of the AB-bonds was introduced. In this case, the multiblock copolymer formed a globule, which had a unique heterogeneous checkerboard-like distribution of the contact density. We discovered that contacts of beads of different types (i.e., AB-contacts) occurred much more frequently than contacts of beads of the same type (i.e., AA- and BB-contacts) in these structures. This effect can be explained by a simple model of chemical equilibrium in a two-component fluid of reversibly interacting particles, which can be solved exactly. This novel type of folding can serve as a basic model for any (AB)k multiblock copolymer chain with a non-vanishing attraction between A and B blocks.

Unavoidable failure of point charge descriptions of electronic density changes for out-of-plane distortions

Population analyses based on point charge approximations accurately estimating the equilibrium dipole moment will systematically fail when predicting infrared intensities of out-of-plane vibrations of planar molecules, whereas models based on both charges and dipoles will always succeed. It is not a matter of how the model is devised but rather how many degrees of freedom are available for the calculation. Population analyses based on point charges are very limited in terms of the amount of meaningful chemical information they provide, whereas models employing both atomic charges and atomic dipoles should be preferred for molecular distortions. A good model should be able to correctly describe not only static, equilibrium structures but also distorted geometries in order to correctly assess information from vibrating molecules. The limitations of point charge models also hold for distortions much larger than those encountered vibrationally.

Theoretical insights into the nature of the semipolar bonds X-O (X=N, P)

Present research is focused on the nature and properties of N-O and P-O bonds in both simple Y3XO molecules (Y=H, F, Cl; X=N, O) and heterocyclic compounds (pyridine, pyridine-N-oxides, phosphorine and phosphorin-1-oxides). Theoretical study has been performed by quantum-chemical calculations with B3LYP/aug-cc-pVTZ method. For the equilibrium structures the electron density distribution was considered by means of topological analysis (QTAIM) as well as analysis in the framework NBO scheme. According to the analysis of both canonical molecular orbitals and NBO for all considered compounds the two pairs of p-orbitals centered on the X and O atoms overlap forms two X-O π-bonds, which together with the X-O σ-bonding allow us to consider X-O as triple bond with almost cylindrical symmetry. For the heterocyclic molecules the influence of the substituents and the nature of the heteroatom on the structure, chemical bonding and aromaticity is discussed.

The structure of equilibria in trading networks with frictions

Several structural results for the set of competitive equilibria in trading networks with frictions are established: The lattice theorem, the rural hospitals theorem, the existence of side‐optimal equilibria, and a group‐incentive‐compatibility result hold with imperfectly transferable utility and in the presence of frictions. While our results are developed in a trading network model, they also imply analogous (and new) results for exchange economies with combinatorial demand and for two‐sided matching markets with transfers.

Accurate equilibrium structures of linear triatomic molecules from a combined theoretical–experimental method: The protonated nitrogen molecule, HN[formula omitted

This article examines several strategies which can be used to derive molecular equilibrium structure from experimental data and extends our previously suggested method to HN2+. Full-dimensional rovibrational calculations are carried out for eight isotopologues of HN2+ using two ab initio potential energy representations. Rovibrational energies computed for rotational angular momenta J as high as 15 in both parities are used to derive theoretical vibration–rotation corrections to ground-state rotation constants B0. These results are combined with the available experimentally derived B0 values to determine the r0, rα, and re structures of the ion. Higher-order corrections beyond the vibration–rotation α constants are found to be essential for the structure determination. Our analysis is supported by graphical representations, illustrating the anticorrelation of the structural parameters. The r0 structure is rationalized in terms of a structure projected onto the principal a axis and examined for the isoelectronic series of linear triatomic molecules HCO+, HCN, HN2+, HNC, and HOC+.

Method for determining of Activation of martensite breakdown during tempering

The method for determining the activation energy of the process of martensite decomposition during tempering of hardened steel is presented. The most equilibrium structure is characterized by the minimum of free energy. The structural organization of such a state is provided by a certain ratio of the surface area of he boundary and the volume of each crystallite, the degree of development of the boundary surface itself, as well as the specific values of the surface energy and chemical potential.

Моделирование механических и физических свойств пучка углеродных нанотрубок при поперечном сжатии с использованием цепной модели с редуцированным числом степеней свободы

The paper studies a bundle of oriented carbon nanotubes (CNTs) under the transverse loading under the plane deformation conditions within the framework of a molecular dynamics model with a reduced number of degrees of freedom. The model takes into account CNT wall stretching and bending, as well as van der Waals interactions. Each CNT is represented by a ring of atoms with two degrees of freedom in the plane of the ring. The discrete nature of the model allows describing the large curvature of the CNT wall and the destruction of CNTs at very high pressure. CNT crystal equilibrium structures are obtained under the strain-controlled biaxial loading. Separate CNTs of a sufficiently large diameter have two equilibrium states: with a round and collapsed cross section. Small-diameter CNTs in the free state can only have a circular cross section. The study identified the presence of two phase transitions observed during biaxial compression of a CNT bundle. The first transformation similar to phase transition of the second order leads to ellipticization of CNT cross sections. As a result of the second transition of the first order, bundled CNTs appear in the beam, the proportion of which gradually increases with the increase in compressive strain. The authors calculated beam elasticity constants such as Young’s moduli, shear modulus, and Poisson’s ratios. The study shows that one of the equilibrium structures (with elliptical CNT cross sections) has the property of a partial auxetic, that is, it has a negative Poisson’s ratio under uniaxial loading in a certain direction. The proposed chain model can be effectively applied to analyze physical and mechanical properties of bundles of single-walled or multi-walled CNTs under the plane deformation conditions, and after simple modifications, it can be used to similar structures made of other two-dimensional nanomaterials.

Физика, химия и механика формирования биоактивных поверхностей на имплантатах. Обзор

The analysis of literature on bioactive surfaces of volume implants and plasma coatings on their surface is made. Influence of the porous sizes on process of growing new bone in an implant surface it is described. The traditional porous structure of a plasma titanic coating is formed due to decrease in extent of deformation of spraying particles on a substrate and it not optimum for growing of a new bone tissue. Modern dense coatings a hydroxyapatite (HA) - the titan have no necessary porous structure, and transfer of cyclic loading through an external layer is not reliable. In too time comparative researches of 17 surfaces of implants at implantation indicate obvious advantages of plasma HA of coatings is not dependent on degree of their crystallinity. Three-dimensional capillary-porous (TCP) titanium coatings in the form of ridges and cavities with additional HA plasma and microplasma coatings are perspective for medical application due to division of dense and porous volumes of a coating, increase in the area of border with a new bone tissue, higher shear and a possibility of spraying of the HA coating with equilibrium structure at a temperature of a surface of titanium at 550 °C. The analysis of HA coating content phase is made depending on the modes of plasma spraying.

Exploiting the "Lego brick" approach to predict accurate molecular structures of PAHs and PANHs.

Polycyclic aromatic hydrocarbons (PAHs) and polycyclic aromatic nitrogen heterocycles (PANHs) are important and ubiquitous species in space. However, their accurate structural and spectroscopic characterization is often missing. To fill this gap, we exploit the so-called "Lego brick" approach [Melli et al., J. Phys. Chem. A, 2021, 125, 9904] to evaluate accurate rotational constants of some astrochemically relevant PAHs and PANHs. This model is based on the assumption that a molecular system can be seen as formed by smaller fragments for which a very accurate equilibrium structure is available. Within this model, the "template molecule" (TM) approach is employed to account for the modifications occurring when going from the isolated fragment to the molecular system under investigation, with the "linear regression" model being exploited to correct the linkage between different fragments. In the present work, semi-experimental equilibrium structures are used within the TM model. The performance of the "Lego brick" approach has been first tested for a set of small PA(N)Hs for which experimental data are available, thus leading to the conclusion that it is able to provide rotational constants with a relative accuracy well within 0.1%. Subsequently, it has been extended to the accurate prediction of the rotational constants for systems lacking any spectroscopic characterization.

Elastocapillary deformation of thin elastic ribbons in 2D foam columns.

The ability of liquid interfaces to shape slender elastic structures provides powerful strategies to control the architecture of mechanical self assemblies. However, elastocapillarity-driven intelligent design remains unexplored in more complex architected liquids – such as foams. Here we propose a model system which combines an assembly of bubbles and a slender elastic structure. Arrangements of soap bubbles in confined environments form well-defined periodic structures, dictated by Plateau's laws. We consider a 2D foam column formed in a container with square cross-section in which we introduce an elastomer ribbon, leading to architected structures whose geometry is guided by a competition between elasticity and capillarity. In this system, we quantify both experimentally and theoretically the equilibrium shapes, using X-ray micro-tomography and energy minimisation techniques. Beyond the understanding of the amplitude of the wavy elastic ribbon deformation, we provide a detailed analysis of the profile of the ribbon, and show that such a setup can be used to grant a shape to a UV-curable composite slender structure, as a foam-forming technique suitable to miniaturisation. In more general terms, this work provides a stepping stone towards an improved understanding of the interactions between liquid foams and slender structures.

Kinetics and thermodynamics of enzymatic decarboxylation of α,β-unsaturated acid: a theoretical study.

Enzymatic decarboxylation of α,β-unsaturated acid through ferulic acid decarboxylase (FDC1) has been of interest because this reaction has been anticipated to be a promising, environmentally friendly industrial process for producing styrene and its derivatives from natural resources. Because the local dielectric constant at the active site is not exactly known, enzymatic decarboxylation to generate β-methylstyrene (β-MeSt) was studied under two extreme conditions (ε = 1 and 78 in the gas phase and aqueous solution, respectively) using the B3LYP/DZP method and transition state theory (TST). The model molecular clusters consisted of an α-methylcinnamate (Cin) substrate, a prenylated flavin mononucleotide (PrFMN) cofactor and all relevant residues of FDC1. Analysis of the equilibrium structures showed that the FDC1 backbone does not play the most important role in the decarboxylation process. The potential energy profiles confirmed that the increase in the polarity of the solvent could lead to significant changes in the energy barriers, especially for the transition states that involve proton transfer. Analysis of the rate constants confirmed the low/no quantum mechanical tunneling effect in the studied temperature range and that inclusion of the fluctuation of the local dielectric environment in the mechanistic model was essential. Because the computed rate constants are not compatible with the time resolution of the stopped-flow spectrophotometric experiment, the direct route for generating β-MeSt after CO2 elimination (acid catalyst (2)) is unlikely to be utilized, thereby confirming that indirect cycloelimination in a low local dielectric environment is the rate determining step. The thermodynamic results showed that the elementary reactions that involve charge (proton) transfer are affected by solvent polarity, thereby leading to the conclusion that overall, the enzymatic decarboxylation of α,β-unsaturated acid is thermodynamically controlled at high ε. The entropy changes due to the generation of molecules in the active site appeared more pronounced than that due to only covalent bond breaking/formation or structural reorientation. This work examined in detail for the first time the scenarios in each elementary reaction and provided insight into the effect of the fluctuations in the local dielectric environment on the enzymatic decarboxylation of α,β-unsaturated acids. These results could be used as guidelines for further theoretical and experimental studies on the same and similar systems.

Statistical Study on the Impact of the New Crown Epidemic on the Supply and Demand Market of Macau Hotel Industry

This paper conducts a systematic study of the market development of the hotel industry in Macau under the influence of the epidemic, and statistically analyzes the changes in supply, demand and prices of the hotel industry from 2020 to 2022. It is found that despite the severe decline in the number of inbound tourists to Macau due to the epidemic, the hotel industry in Macau has maintained a relatively stable situation, as evidenced by a small increase in the number of hotel and room operations and an occupancy rate that basically remains at the only major decline was in hotel prices. By analyzing the reasons for the changes in the Macau hotel market in various aspects, a supply and demand equilibrium structure of the Macau hotel market is constructed based on the price equilibrium theory, which can provide a reference for the rapid recovery of the hotel economy in various regions in the post-epidemic era.

Study of transition metal dichalcogenides/chromium trihalides van der Waals heterostructure by band unfolding method

The transition metal dichalcogenides <i>MX</i><sub>2</sub>/Chromium Trihalides Cr<i>X</i><sub>3</sub> van der Waals heterostructures can control the valley polarization of of <i>MX</i><sub>2</sub> effectively, which makes them possess promising potential applications in valleytronics. In the present work, the stacking order and electronic structure of MoSe<sub>2</sub>/CrI<sub>3</sub>, MoSe<sub>2</sub>/CrBr<sub>3</sub> and WS<sub>2</sub>/CrBr<sub>3</sub> are investigated based on the first-principle calculation and k-projection band unfolding method. The underlying mechanism of valley splitting is also explored. The stacking energy surfaces are calculated and the stable stacking configurations are determined. The effects of the breaking of time-symmetry and spatial-symmetry on electronic structure are also revealed. Because of the orbital hybridization, the conduction band of heterostructure becomes complicated and the valence band maximum changes drastically. It is thus difficult to compare the electronic structure of vdW heterostructure with that of free-standing <i>MX</i><sub>2</sub> directly. Through the unfolding energy band, the electronic structure change of <i>MX</i><sub>2</sub> induced by Cr<i>X</i><sub>3</sub> is revealed clearly, and the valley splitting of <i>MX</i><sub>2</sub> is obtained quantitatively. Moreover, the interlayer distance and strain are found to be able to tune the valley splitting effectively. When the interlayer distance reduces to 2.6 Å, the valley splitting of MoSe<sub>2</sub>/CrI<sub>3</sub> is enhanced to 10.713 meV with the increase of <i>AB</i> stacking, which is 8.8 times as large as the value of equilibrium structure. This work breaks through the limit of the complex electronic structure in supercell, providing an important reference for studying other magnetic vdW heterostructure.

Determination of the semiexperimental equilibrium structure of 2-acetylthiophene in the presence of methyl internal rotation and substituent effects compared to thiophene.

The microwave spectra of thiophene and 2-acetylthiophene were recorded in the frequency range from 2 to 40 GHz using two molecular jet Fourier transform microwave spectrometers. For 2-acetylthiophene, two conformers with a syn and an anti orientation of the S1-C2 and C6O bonds (with respect to the C2-C6 bond) were identified, and the syn-conformer was more stable. The spectra of the 34S- and 13C-isotopologues of syn-2-acetylthiophene were also assigned, and the semiexperimental equilibrium structure could be determined. Compared to thiophene, at the substitution position, the S1-C2 and C2C3 bond lengths both increase by about 0.007 Å, and the bond angle S1-C2C3 decreases by 0.06°, noticeably larger than the experimental uncertainties. A-E torsional splittings were observed due to internal rotation of the methyl group hindered by a barrier height of 330.187(35) and 295.957(17) cm-1 for the syn-conformer and the anti-conformer, respectively. Geometry and internal rotation parameters are compared with those of related thiophene derivatives, as well as those of furan and 2-acetylthiophene to gain a better understanding of structure determination in the presence of methyl internal rotation.